ArticleMolecular oncology2020
Mislocalized cytoplasmic p27 activates PAK1-mediated metastasis and is a prognostic factor in osteosarcoma.
Article in Molecular oncology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.
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Who cites it
11 citing papers in PubMed, 1 synthesis or guideline pooled it, 17 citations in OpenAlex.
- p27Histology and histopathology · 2025Pooled it
- A Spatiotemporal Model of CXCL10 as a Master Regulator of Immune Evasion and Metastasis in Osteosarcoma.International journal of molecular sciences · 2025Review
- The metastatic role of the CXCL10-CXCR3 axis and its therapeutic potential in osteosarcoma.Journal of bone oncology · 2025Article
- CIP/KIP and INK4 families as hostages of oncogenic signaling.Cell division · 2024Review
- Review
- LOX upregulates FAK phosphorylation to promote metastasis in osteosarcoma.Genes & diseases · 2023Article
- Knockdown of lncRNA LINC00662 suppresses malignant behaviour of osteosarcoma cells via competition with miR-30b-3p to regulate ELK1 expression.Journal of orthopaedic surgery and research · 2022Article
- Osteosarcoma of the Mandible in an Elderly Patient.Case reports in dentistry · 2022Article
- The promising effects of BMP2 transfected mesenchymal stem cells on human osteosarcoma.Turkish journal of biology = Turk biyoloji dergisi · 2021Article
- Comprehensive analysis of prognostic tumor microenvironment-related genes in osteosarcoma patients.BMC cancer · 2020Article
- P21-Activated Kinase 1: Emerging biological functions and potential therapeutic targets in Cancer.Theranostics · 2020Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
The development of pulmonary metastasis is the leading cause of death in osteosarcoma (OS), which is the most common malignant bone tumor in children. We have previously reported that the tumor suppressor p27 (KIP1, CDKN1B) is frequently mislocalized to the cytoplasm of OS. However, its prognostic significance and metastatic mechanism are still elusive. Here, we show that cytoplasmic p27 significantly correlated with a higher metastatic status and poorer survival of OS patients (n = 136, P < 0.05), highlighting the clinical significance of p27 mislocalization in OS. Mechanistically, cytoplasmic p27 is co-immunoprecipitated with p21-activated kinase 1 (PAK1), which resulted in higher PAK1 phosphorylations, actin polymerization, and cell motility in p27-mislocalized OS cells. Silencing PAK1 expression in different p27-mislocalized OS cell lines decreased the migratory and adhesion abilities in vitro, as well as the development of pulmonary metastases in vivo. Similar PAK1-dependent motility was also observed in other p27-mislocalized cancer cell lines. In summary, our study suggests that cytoplasmic p27-mediated PAK1 activation is crucial for OS metastasis. A biomarker-guided targeted therapeutic approach for metastatic OS and other cancers harboring p27 mislocalization can be developed, where cytoplasmic p27 is used for risk stratification and PAK1 can be exploited as a potential therapeutic target.
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